Deletion of the Histone Deacetylase HdaA in Endophytic Fungus <i>Penicillium chrysogenum</i> Fes1701 Induces the Complex Response of Multiple Bioactive Secondary Metabolite Production and Relevant Gene Cluster Expression
Epigenetic regulation plays a critical role in controlling fungal secondary metabolism. Here, we report the pleiotropic effects of the epigenetic regulator HdaA (histone deacetylase) on secondary metabolite production and the associated biosynthetic gene clusters (BGCs) expression in the plant endop...
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MDPI AG
2020-08-01
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| Series: | Molecules |
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| author | Zhuang Ding Haibo Zhou Xiao Wang Huiming Huang Haotian Wang Ruiyan Zhang Zhengping Wang Jun Han |
| author_facet | Zhuang Ding Haibo Zhou Xiao Wang Huiming Huang Haotian Wang Ruiyan Zhang Zhengping Wang Jun Han |
| author_sort | Zhuang Ding |
| collection | DOAJ |
| description | Epigenetic regulation plays a critical role in controlling fungal secondary metabolism. Here, we report the pleiotropic effects of the epigenetic regulator HdaA (histone deacetylase) on secondary metabolite production and the associated biosynthetic gene clusters (BGCs) expression in the plant endophytic fungus <i>Penicillium chrysogenum</i> Fes1701. Deletion of the <i>hdaA</i> gene in strain Fes1701 induced a significant change of the secondary metabolite profile with the emergence of the bioactive indole alkaloid meleagrin. Simultaneously, more meleagrin/roquefortine-related compounds and less chrysogine were synthesized in the <i>ΔhdaA</i> strain. Transcriptional analysis of relevant gene clusters in <i>ΔhdaA</i> and wild strains indicated that disruption of <i>hdaA</i> had different effects on the expression levels of two BGCs: the meleagrin/roquefortine BGC was upregulated, while the chrysogine BGC was downregulated. Interestingly, transcriptional analysis demonstrated that different functional genes in the same BGC had different responses to the disruption of <i>hdaA</i>. Thereinto, the <i>roqO</i> gene, which encodes a key catalyzing enzyme in meleagrin biosynthesis, showed the highest upregulation in the <i>ΔhdaA</i> strain (84.8-fold). To our knowledge, this is the first report of the upregulation of HdaA inactivation on meleagrin/roquefortine alkaloid production in the endophytic fungus <i>P. chrysogenum</i>. Our results suggest that genetic manipulation based on the epigenetic regulator HdaA is an important strategy for regulating the productions of secondary metabolites and expanding bioactive natural product resources in endophytic fungi. |
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| spelling | doaj.art-6908e9498e794dacba037b92e96bd77a2023-11-20T09:47:27ZengMDPI AGMolecules1420-30492020-08-012516365710.3390/molecules25163657Deletion of the Histone Deacetylase HdaA in Endophytic Fungus <i>Penicillium chrysogenum</i> Fes1701 Induces the Complex Response of Multiple Bioactive Secondary Metabolite Production and Relevant Gene Cluster ExpressionZhuang Ding0Haibo Zhou1Xiao Wang2Huiming Huang3Haotian Wang4Ruiyan Zhang5Zhengping Wang6Jun Han7Institute of BioPharmaceutical Research, Liaocheng University, Liaocheng 252059, ChinaShandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, ChinaInstitute of BioPharmaceutical Research, Liaocheng University, Liaocheng 252059, ChinaSchool of Life Science, Liaocheng University, Liaocheng 252059, ChinaFaculty of Pharmacy, Bengbu Medical College, Bengbu 233000, ChinaInstitute of BioPharmaceutical Research, Liaocheng University, Liaocheng 252059, ChinaInstitute of BioPharmaceutical Research, Liaocheng University, Liaocheng 252059, ChinaInstitute of BioPharmaceutical Research, Liaocheng University, Liaocheng 252059, ChinaEpigenetic regulation plays a critical role in controlling fungal secondary metabolism. Here, we report the pleiotropic effects of the epigenetic regulator HdaA (histone deacetylase) on secondary metabolite production and the associated biosynthetic gene clusters (BGCs) expression in the plant endophytic fungus <i>Penicillium chrysogenum</i> Fes1701. Deletion of the <i>hdaA</i> gene in strain Fes1701 induced a significant change of the secondary metabolite profile with the emergence of the bioactive indole alkaloid meleagrin. Simultaneously, more meleagrin/roquefortine-related compounds and less chrysogine were synthesized in the <i>ΔhdaA</i> strain. Transcriptional analysis of relevant gene clusters in <i>ΔhdaA</i> and wild strains indicated that disruption of <i>hdaA</i> had different effects on the expression levels of two BGCs: the meleagrin/roquefortine BGC was upregulated, while the chrysogine BGC was downregulated. Interestingly, transcriptional analysis demonstrated that different functional genes in the same BGC had different responses to the disruption of <i>hdaA</i>. Thereinto, the <i>roqO</i> gene, which encodes a key catalyzing enzyme in meleagrin biosynthesis, showed the highest upregulation in the <i>ΔhdaA</i> strain (84.8-fold). To our knowledge, this is the first report of the upregulation of HdaA inactivation on meleagrin/roquefortine alkaloid production in the endophytic fungus <i>P. chrysogenum</i>. Our results suggest that genetic manipulation based on the epigenetic regulator HdaA is an important strategy for regulating the productions of secondary metabolites and expanding bioactive natural product resources in endophytic fungi.https://www.mdpi.com/1420-3049/25/16/3657metabolic regulationroquefortinemeleagrinendophytic fungi<i>Penicillium chrysogenum</i> |
| spellingShingle | Zhuang Ding Haibo Zhou Xiao Wang Huiming Huang Haotian Wang Ruiyan Zhang Zhengping Wang Jun Han Deletion of the Histone Deacetylase HdaA in Endophytic Fungus <i>Penicillium chrysogenum</i> Fes1701 Induces the Complex Response of Multiple Bioactive Secondary Metabolite Production and Relevant Gene Cluster Expression Molecules metabolic regulation roquefortine meleagrin endophytic fungi <i>Penicillium chrysogenum</i> |
| title | Deletion of the Histone Deacetylase HdaA in Endophytic Fungus <i>Penicillium chrysogenum</i> Fes1701 Induces the Complex Response of Multiple Bioactive Secondary Metabolite Production and Relevant Gene Cluster Expression |
| title_full | Deletion of the Histone Deacetylase HdaA in Endophytic Fungus <i>Penicillium chrysogenum</i> Fes1701 Induces the Complex Response of Multiple Bioactive Secondary Metabolite Production and Relevant Gene Cluster Expression |
| title_fullStr | Deletion of the Histone Deacetylase HdaA in Endophytic Fungus <i>Penicillium chrysogenum</i> Fes1701 Induces the Complex Response of Multiple Bioactive Secondary Metabolite Production and Relevant Gene Cluster Expression |
| title_full_unstemmed | Deletion of the Histone Deacetylase HdaA in Endophytic Fungus <i>Penicillium chrysogenum</i> Fes1701 Induces the Complex Response of Multiple Bioactive Secondary Metabolite Production and Relevant Gene Cluster Expression |
| title_short | Deletion of the Histone Deacetylase HdaA in Endophytic Fungus <i>Penicillium chrysogenum</i> Fes1701 Induces the Complex Response of Multiple Bioactive Secondary Metabolite Production and Relevant Gene Cluster Expression |
| title_sort | deletion of the histone deacetylase hdaa in endophytic fungus i penicillium chrysogenum i fes1701 induces the complex response of multiple bioactive secondary metabolite production and relevant gene cluster expression |
| topic | metabolic regulation roquefortine meleagrin endophytic fungi <i>Penicillium chrysogenum</i> |
| url | https://www.mdpi.com/1420-3049/25/16/3657 |
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